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The cytochrome P450 pathway in angiogenesis and endothelial cell biology

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Abstract

Long thought to be biologically important only as xenobiotic metabolizing enzymes, it is now clear that extrahepatic cytochrome P450 epoxygenases can utilize endogenous substrates such as arachidonic acid, linoleic acid, eicosapentaenoic acid, and docosahexaenoic acid to generate bioactive lipid mediators. The epoxides thus generated can acutely affect vascular tone, and stimulate a spectrum of signaling pathways that affect growth-promoting kinase and transcription factor activity in vascular as well as cancer cells. Endogenous epoxide levels are largely controlled by the activity of the soluble epoxide hydrolase, and specific inhibitors of the enzyme as well as knockout mice are helping to determine the roles of these lipids in physiological and pathological angiogenesis. This review summarizes current knowledge on the aspects of the cytochrome P450/soluble epoxide hydrolase pathway related to vascular homeostasis and cancer.

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Acknowledgments

We apologize to the many scientists whose work could not be cited because of space constraints. The author’s own work was supported by the Deutsche Forschungsgemeinschaft (TR-SFB 23/A6 and Exzellenzcluster 147 “Cardio-Pulmonary Systems”).

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  1. Institute for Vascular Signalling, Centre for Molecular Medicine, Johann Wolfgang Goethe University Frankfurt, Theodor-Stern-Kai 7, 60590, Frankfurt am Main, Germany

    Ingrid Fleming

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Fleming, I. The cytochrome P450 pathway in angiogenesis and endothelial cell biology. Cancer Metastasis Rev 30, 541–555 (2011). https://doi.org/10.1007/s10555-011-9302-3

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